儿童慢性鼻窦炎基因表达谱的生物信息学分析  

Bioinformatics analysis of gene expression profile in pediatric patients with chronic rhinosinusitis

作　　者：李琳 高正文 崔楠 孙健平 黄贤明 崔静 LI Lin;GAO Zhengwen;CUI Nan;SUN Jianping;HUANG Xianming;CUI Jing(Department of Otolaryngology,Qingdao Women and Children's Hospital,Qingdao 266011,Shandong,China;Department of Anesthesiology,Guzhen Orthopedic Hospital of Chengyang,Qingdao 266000,Shandong,China;Hospital Management Institute,The Affiliated Hospital of Qingdao University,Qingdao 266003,Shandong,China;Qingdao Municipal Center for Disease Control and Prevention/Qingdao Institute of Preventive Medicine,Qingdao 266033,Shandong,China;Department of Surgery,Qingdao Haici Medical Group,Qingdao 266000,Shandong,China)

机构地区：[1]青岛市妇女儿童医院耳鼻喉科,山东青岛266011 [2]青岛城阳古镇正骨医院麻醉科,山东青岛266000 [3]青岛大学附属医院医院管理研究所,山东青岛266003 [4]青岛市疾病预防控制中心/青岛市预防医学研究院,山东青岛266033 [5]青岛市海慈医疗集团外科,山东青岛266000

出　　处：《山东大学耳鼻喉眼学报》2022年第3期171-180,共10页Journal of Otolaryngology and Ophthalmology of Shandong University

基　　金：青岛市科技局立项(19-6-1-5-nsh);青岛市2017年度医药科研指导计划(2017-WJZD129、2017-WJZD134);青岛市医疗卫生优秀人才培养项目。

摘　　要：目的从基因水平上探讨儿童慢性鼻窦炎(CRS)可能的分子生物学机制,为儿童CRS的防治提供理论依据。方法通过GEO Datasets数据库获取儿童CRS的基因表达谱GSE10406数据集,并筛选儿童CRS组与正常对照组的鼻窦黏膜组织上差异表达基因(DEGs),采用DAVID及GSEA对DEGs进行基因本体论(GO)分析和KEGG信号通路分析,采用String在线软件和Cytoscape软件对DEGs进行蛋白互作网络构建分析。结果以校正后的P值<0.05且∣log2 FC∣>2为标准共筛选出儿童CRS相关的DEGs有92个,其中57个上调DEGs,35个下调DEGs。GO分析结果显示上调的DEGs显著富集在吞噬作用、β细胞受体信号通路、对细菌的防御反应、免疫应答、浆膜外等生物学进程,KEGG分析显示上调的DEGs富集在唾液分泌等信号通路,下调的DEGs显著富集在视黄醇代谢、化学致癌、酪氨酸代谢等信号通路。PPI分析结果显示,49个儿童CRS相关DEGs参与了网络构建,该蛋白网络共有61条边,蛋白评价节点度为1.51,局部聚类系数为0.387,蛋白互作网络差异有统计学意义(P<0.001),前10位的关键基因分别为ASPM、NCAPG、TPX2、MCM10、TOP2A、STATH、ADH1C、ADH6、CYP26A1、UGT2A2。除STATH,其余9个关键基因编码的蛋白均在MCODE模块1和模块2中。结论儿童CRS可能通过其关键基因调节白介素、炎症、免疫反应、β细胞受体信号通路、对细菌的防御、唾液分泌等一系列生物学进程来影响其发生发展,可能的分子生物学机制需要进一步的探讨。Objective We performed a preliminary bioinformatics analysis of genes from pediatric patients with chronic rhinosinusitis(CRS)to provide a scientific basis for preventing and treating CRS.Methods Data of pediatric patients with CRS were downloaded from Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were screened in sinus mucosa tissue from pediatric patients with CRS and normal children.DEGs associated with the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway were analyzed using the DAVID tool and Gene Set Enrichment Analysis(GESA).Protein-protein interaction(PPI)network associated with DEGs were analyzed using STRING and Cytoscape.Results Ninety-two DEGs were screened using adjusted P<0.05 and∣log2 FC∣>2.Of these DEGs,57 were up-regulated,and 35 were down-regulated.GO analysis showed that up-regulated DEGs were enriched in phagocytosis,βcell receptor signaling pathway,bacterial defense response,immune response,and the external side of the plasma membrane.KEGG pathway analysis showed that up-regulated DEGs were enriched in salivary secretion,and down-regulated DEGs were enriched in retinol metabolism,chemical carcinogenesis,and tyrosine metabolism.All 49 DEGs were involved in the PPI network,with 61 edges,an average protein node degree of 1.51,and a local clustering coefficient of 0.387.The PPI enrichment had a significant difference(P<0.001).The top 10 hub genes were ASPM,NCAPG,TPX2,MCM10,TOP2A,STATH,ADH1C,ADH6,CYP26A1,and UGT2A2.Except for STATH,the hub genes were all in Modules 1 and 2.Conclusion The CRS pathogenesis in pediatric patients is mediated by interleukins,inflammation,immune response,βcell receptor signaling pathway,salivary secretion,and bacterial defense response by hub genes.Further studies are required to explore the putative mechanisms in pediatric patients with CRS.

关 键 词：慢性鼻窦炎 儿童 基因本体学论分析 KEGG 分析 蛋白互作网络分析 

分 类 号：R765.4[医药卫生—耳鼻咽喉科]